Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Hagemeijer, F.

Calcium sensitization with pimobendan: pharmacology, haemodynamic improvement, and sudden death in patients with chronic congestive heart failure.

Calcium sensitization increases myocardial contractility by improving energy utilization of the myocardium, without an increase in intracellular concentrations of cyclic adenosine monophosphate. The calcium sensitizer most extensively studied up to now is pimobendan (UD-CG 115 BS). Vasodilatation results primarily from phosphodiesterase III inhibition. Orally administered pimobendan appears rapidly in plasma. A peak concentration is reached 1.5 h after drug intake; elimination from the plasma compartment has a half-life of 1.5 h. First-pass hepatic O-desmethylation of pimobendan produces the active metabolite UD-CG 212; plasma concentration curves of UD-CG 212 are similar to those of pimobendan, with a peak concentration 1-2 h later than the peak concentration of the parent compound. In patients with chronic congestive heart failure, pimobendan produces a dose-dependent and prolonged decrease in pulmonary capillary wedge pressure and an increase in cardiac output. Maintenance doses of pimobendan are well tolerated and may lead to lasting symptomatic improvement in patients with heart failure; open and blinded trials show that exercise tolerance increases. No attenuation of these effects is seen during long-term therapy with pimobendan. Patients in chronic congestive heart failure frequently die suddenly; many inotropic agents increase the incidence of sudden death in these patients. Although proarrhythmia has never been observed with pimobendan, arrhythmia suppression with amiodarone seems prudent in heart failure patients receiving maintenance doses of pimobendan.[1]

References

Calcium sensitization with pimobendan: pharmacology, haemodynamic improvement, and sudden death in patients with chronic congestive heart failure. Hagemeijer, F. Eur. Heart J. (1993) [Pubmed]

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